4. Discussion
Since the emergence of SARS-CoV-2 at the end of 2019, a broad range of strategies, notably NPIs, have been globally implemented to combat the virus. These measures, including city lockdowns, social distancing, use of personal protective equipment, and enhanced hygiene practices, have substantially reduced coronavirus transmission. The application of NPIs has notably interrupted the usual seasonal patterns of common respiratory viruses. A marked decrease in influenza and Respiratory Syncytial Virus (RSV) cases was observed following NPI implementation[21]. In contrast, Rhinovirus (RV) infections exhibited an increasing trend. This is supported by studies from New Zealand, which reported a high incidence of RV infection during the pandemic[22]. Furthermore, a study in Suzhou, China, involving 10,396 viral respiratory infection cases, identified RV as the most frequently detected virus, accounting for 23.3% of infections[23]. Between January 2021 and December 2023, our study included 19,680 pediatric inpatients with ARTIs. Of these, 21.55% tested positive for RV, peaking in April 2021 and November 2022. A year-on-year decrease in RV infections was noted, declining from 24.36% in 2021 to 19.67% in 2023. Seasonal fluctuations in RV infections aligned with existing literature, demonstrating a higher prevalence in autumn, winter, and spring. The study observed that the 0-1 year age group had the highest proportion of RV infections. Significant variations in infection rates across different age groups were noted, predominantly in children under three years. Phylogenetic analysis revealed 23 distinct RV subtypes, with RV-A and RV-C being the most common. A significant shift in the dominance between RV-A and RV-C in 2022 indicated a dynamic pattern in RV circulation and genetic diversity. The study also investigated the correlation between RV subtypes and clinical characteristics, finding a predominance of RV-C in asthmatic patients and a higher incidence of severe RV-associated Lower Respiratory Tract Infections (LRTIs) in males. This study explores the epidemiological shifts in RV infections among children on Hainan Island, emphasizing the effects of the termination of the zero-COVID policy in a region with distinct climatic and geographical characteristics.
In March and August 2022, Hainan, China, experienced two COVID-19 pandemic. In response, strict NPIs were enforced throughout the year, until the lifting of zero-COVID policies. Despite the implementation of preventive measures, a significant reduction in RV infections was not evident, suggesting that the efficacy of face masks in curbing RV transmission might have diminished during this period. RV is a non-enveloped virus known for its relative resistance to disinfectants containing ethanol and its ability to survive on environmental surfaces for extended periods transmission[4, 5]. While medical masks are effective in blocking large droplets and aerosols, they may not provide adequate protection against smaller particles like RV. This may also be one of the main reasons why RV infection rates remained high during the COVID-19 epidemic. Notably, with the advent of the Omicron variant and a substantial increase in vaccination rates, governments worldwide have begun to roll back these stringent measures, aiming to normalize social activities. This policy shift has led to an increase in reports of respiratory virus resurgence[20]. According to monitoring by the World Health Organization, after a significant reduction in the transmission of respiratory viruses globally during the COVID-19 pandemic, there has been a marked increase in the activity level of respiratory viruses across the world [22]. On 7 December 2022, China’s modification of the dynamic zero-COVID-19 policy precipitated a widespread outbreak of COVID-19 in the following months. This alteration, together with the relaxation of non-pharmaceutical interventions (NPIs) and social distancing measures, is presumed to have impacted the epidemiology of other respiratory tract infections. Particularly, an increase in influenza A virus infections among children was noted in Shanghai after the policy change[17]. The concept of viral interference, involving interactions between influenza virus, rhinovirus, and other respiratory viruses, is a plausible factor in the decreased prevalence of RV infections observed in pediatric inpatients with ARTIs in 2023. This suggests a complex interplay of viral interactions within the evolving public health context.
The study demonstrated that, during the COVID-19 epidemic period, RV infection rates on Hainan Island were highest in children under three years old. Furthermore, the prevalence of RV infections diminished progressively with increasing age. This trend is likely due to the development of cumulative immunity from repeated exposure to diverse RV serotypes. Notably, a substantial number of RV cases were recorded in children under three, with toddlers being particularly prone to infection. Given the elevated infection rates in this demographic, our findings underscore the importance of targeted prevention and healthcare strategies. Effective measures include enhancing hygiene practices, advancing vaccination efforts, and educating parents and caregivers about RV risks and preventive methods, aiming to alleviate the disease’s impact on young children. Our investigation further identified a notable gender-based disparity in RV infection rates, exhibiting a predominance in male children. This observation contrasts with certain earlier reports. Specifically, Haixia Jiang et al. analyzed 5,832 nasopharyngeal swabs collected from patients with acute respiratory infections spanning 2012 to 2020, finding a RV infection rate of 2.74% (160/5832), with no significant gender disparity in the patient cohort[5]. Similarly, a study by Wanwei Li, Lili et al., which examined nasopharyngeal swabs from 655 patients suffering from ARTIs, also reported no significant gender difference among those infected with rhinovirus [6]. This divergence in findings underscores the complexity of RV transmission dynamics and suggests the influence of additional, possibly region-specific, factors affecting susceptibility and infection rates among different demographics.
Seasonal variation, characterized by changes in humidity, temperature, and climate, serves as an external factor that can significantly influence the severity of viral illnesses. Studies on rhinovirus (RV) patterns in different climatic conditions reveal contrasting findings: while RV detection peaks during the rainy seasons in Malaysia and Latin America, increased RV activity is observed in the dry seasons of Brazil and Cambodia. The RV infections predominantly occurred in autumn, winter, and spring on Hainan Island. Given its tropical setting, the island experiences its rainy season from May to October, suggesting a complex relationship between seasonal patterns and RV infection rates, which may not solely depend on precipitation levels.
Phylogenetic analysis identified three RV species among the positive samples: RV-A (46.88%), RV-B (6.25%), and RV-C (46.88%) in Hainan Island. It was found that RV-A and RV-C are the primary strains transmitting rhinovirus on Hainan Island, with multiple types circulating simultaneously. Our study highlighted a significant temporal transition in RV strain dominance, with RV-C surpassing RV-A to become the predominant strain starting in October 2022. This shift coincided with a peak in RV infection rates in November 2022, the highest observed in the past three years, potentially linked to specific epidemic strain subtypes and variations in annual weather patterns. Additionally, international research highlights significant genotype variations in circulating rhinoviruses, related to both time and geographical factors[24, 25]. The consistent identification and seasonal variation in the dominance of RV-A and RV-C strains across these studies reflect our findings, emphasizing the prevailing influence of these strains.
Previous studies have suggested that RV-C might play a role in severe clinical disease [26]. RV-C was present in the majority of children with acute asthma and was associated with more severe asthma[27, 28]. Wheezing episodes were also more common among individuals with RV-C and RV-A infection than among those with RV-B infection[26]. Another study suggested that RV-C was associated with more severe disease in children <3 years of age[29]. However, some reports found no differences in the clinical characteristics among hospitalized enrolled patients positive for RV-A, RV-B, or RV-C, including wheezing[30]. In our study, we observed that patients infected with RV-A tended to be younger compared to patients infected with RV-C. Additionally, we also noted that children infected with RV-C were more likely to exhibit clinical symptoms of wheezing. These findings suggest that there are differences in age distribution and clinical presentation between RV-A and RV-C. In our analysis, patients were divided into groups based on the severity of Lower Respiratory Tract Infections (LRTIs), showing no significant age-related differences between these categories. Notably, a greater occurrence of severe RV-associated LRTIs was identified in males, with 85.71% of severe cases found in boys, introducing potential gender-specific variations in disease severity. Additionally, the study revealed that children with asthma histories were more susceptible to severe LRTIs and extended hospitalizations, supporting the theory that pre-existing respiratory conditions can amplify RV infection impacts[31, 32]. This emphasizes the importance of vigilant monitoring and possibly specialized treatment approaches for asthmatic children with RV infections.
This study faces several limitations that merit attention. Firstly, all samples were sourced exclusively from Hainan Maternal and Child Health Hospital, the largest tertiary pediatric hospital in Hainan, which predominantly treats severe cases of childhood illnesses. While this facility’s prominence lends weight to our findings, the single-center nature of the analysis introduces potential biases, as it may not fully represent the broader pediatric population of Hainan Island. Secondly, RV subtypes were identified in only 32 RV-positive samples collected at different times. This sample size is too limited to comprehensively reflect the variety of RV subtypes circulating across Hainan Island. Future studies that include a wider range of collection sites encompassing more hospitals and regions on Hainan Island, along with an expanded analysis of RV subtypes, are crucial for a more complete understanding of the epidemiology of RV infections in this area.